Compatibility mechanism of Weichang’an formula and its disassembled formulas in inhibiting the growth and metastasis of orthotopic transplanted human gastric cancer in nude mice based on MMP-2 and MMP-9 expression
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Compatibility mechanism of Weichang’an formula and its disassembled formulas in inhibiting the growth and metastasis of orthotopic transplanted human gastric cancer in nude mice based on MMP-2 and MMP-9 expression
Shanghai Journal of Traditional Chinese MedicineVol. 54, Issue 9, Pages: 81-87(2020)
PAN Chuanfang, LIANG Weimo, GU Xian, et al. Compatibility mechanism of Weichang’an formula and its disassembled formulas in inhibiting the growth and metastasis of orthotopic transplanted human gastric cancer in nude mice based on MMP-2 and MMP-9 expression. [J]. Shanghai Journal of Traditional Chinese Medicine 54(9):81-87(2020)
DOI:
PAN Chuanfang, LIANG Weimo, GU Xian, et al. Compatibility mechanism of Weichang’an formula and its disassembled formulas in inhibiting the growth and metastasis of orthotopic transplanted human gastric cancer in nude mice based on MMP-2 and MMP-9 expression. [J]. Shanghai Journal of Traditional Chinese Medicine 54(9):81-87(2020) DOI: 10.16305/j.1007-1334.2020.1911187.
Compatibility mechanism of Weichang’an formula and its disassembled formulas in inhibiting the growth and metastasis of orthotopic transplanted human gastric cancer in nude mice based on MMP-2 and MMP-9 expression
Objective:To explore the effects and compatibility regularity of Weichang’an recipe (WCAR)and its disassembled recipes with different efficacious components on the growth and metastasis of orthotopic transplanted tumor in nude mice with gastric cancer in vivo. MethodsAccording to its efficacy, WCAR was divided into three components: Jianpi Liqi (JPLQ, invigorating spleen and regulating qi), Qinre Jiedu(QRJD, clearing away heat and removing toxin) and Ruanjian Sanjie(RJSJ, softening hardness and dissipating mass). A 2*2*2 factorial experiment was designed to establish an orthotopic transplantation model of human gastric cancer in nude mice and to observe the effects of different effective components of WCAR on inhibiting the growth and metastasis of gastric cancer and whether there is interaction between them. Results:①The tumor inhibition rates of the WCAR group, the JPLQ group, the RJSJ group and the Jianpi Qingre(JPQR, invigorating spleen and clearing away heat) group were 28.5%, 24.6%, 28.8% and 30.2%, respectively.The tumor weight in these groups were significantly reduced compared with the model group(P<0.05).The factor of the RJSJ had the main effect in inhibiting the weight of tumor, and there was an interaction between the JPLQ factor and the RJSJ factor.②The metastasis rates of the WCAR group, QRJD group and JPQR group were 22.22%, 10.00% and 18.18% respectively, which were obviously reduce the metastasis rate of gastric cancer in nude mice compared with 75% of model control group(P<0.05).③The expression of MMP-2 protein was inhibited in the WCAF group and its disassembled recipe groups except the RJSJ group,especially in the JPLQ group and the WCAR group(P<0.05). There was the most obvious inhibitory effect on the expression of MMP-9 protein in the Jianpi(JP, invigorating spleen) group, JPQR group and WCAR group(P<0.05).The results of factorial analysis showed that in the presence of RJSJ factor, the factors of JPLQ and QRJD had a synergistic effect on down-regulating the expression of MMP-2 protein.The WCAF and its disassembled recipes could inhibit the expression of MMP-2 gene in gastric tumor tissue of nude mice in varying degrees, especially in the WCAR group, Jianpi Ruanjian(JPRJ, invigorating spleen and softening hardness) group and Qingre Ruanjian(QRRJ, clearing away heat and softening hardness) group(P<0.01). The results showed that there was interaction between the group of JPLQ combined with QRJD and the group of QRJD combined with RJSJ on the inhibition of MMP-2 gene expression. The WCAR group and JPRJ group had obvious inhibitory effect on the expression of MMP-9 mRNA in gastric tumor tissue of nude mice(P<0.01). The factor of JPLQ combined with QRJD and the factor of JPLQ combined with RJSJ had interactive effect on the inhibition of MMP-9 mRNA expression.The WCAF group and JPLQ group significantly inhibited the activities of MMP-2 and MMP-9 in gastric tumor tissue of nude mice(P<0.01).The results of factorial analysis showed that in the presence of QRJD factor, the factors of JPLQ and RJSJ had a synergistic effect in inhibiting the activities of MMP-2 and MMP-9, while in the absence of QRJD factor, The JPLQ and RJSJ factors had antagonistic effects in inhibiting MMP-2 and MMP-9 activities. Conclusion:The WCAR group, QRJD group has JPQR group cansignificantly inhibit the growth and metastasis of gastric cancer in nude mice, and the QRJD group has the most obvious inhibitory effect on the metastasis of gastric cancer. The JPLQ factor has significant inhibitory effect on tumor weight and the factors of JPLQ and RJSJ have interaction in inhibiting tumor weight.The results of factorial analysis show that JPLQ and QRJD factors have a synergistic effect on down-regulating the expression of MMP-2 protein in the presence of RJSJ factor, and the factors of JPLQ and QRJD had antagonistic effect on the down-regulation of MMP-2 protein expression in the absence of RJSJ factor. In the presence of QLJD factor, JPLQ and RJSJ factors have a synergistic effect on inhibiting the activities of MMP-2 and MMP-9, while in the absence of QLJD factor, JPLQ and RJSJ factors have antagonistic effects on the inhibition of MMP-2 and MMP-9 activities.
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